vanucizumab (RG7221) / Roche - LARVOL DELTA

Multilevel─Intact, Subunits, and Peptides─Characterization of Antibody-Based Therapeutics by a Single-Column LC-MS Setup. (PubMed, Anal Chem) - "In this study, we developed a robust middle-down LC-MS method on a ZenoTOF 7600 and evaluated a C4 LC-MS setup for the characterization of NISTmAb, RG7221 bispecific antibody (bsAb), and Fc-fusion etanercept by intact protein, subunit middle-up/down, and bottom-up analyses. This is also the first report on middle-down analysis of the major etanercept TNFR and Fc subunit glycoforms. A streamlined single-column LC-MS setup will enable more robust and efficient MS workflows for PQA assessment and simplify the integration of an LC-MS analyzer as a process analytical technology instrument for biopharma applications."

Journal

Predictive potential of angiopoietin-2 in a mCRC subpopulation treated with vanucizumab in the McCAVE trial. (PubMed, Front Oncol) - P2 | "The potential benefit of combined inhibition of Ang-2 and VEGF-A in previously untreated patients with mCRC was evaluated in the phase II McCAVE study (NCT02141295), assessing vanucizumab versus bevacizumab (VEGF-A inhibitor), both in combination with mFOLFOX-6 (modified folinic acid [leucovorin], fluorouracil and oxaliplatin) chemotherapy. These data suggest that Ang-2 may be both a prognostic biomarker in mCRC and a predictive biomarker for vanucizumab in KRAS wild-type mCRC. Thus, this evidence can potentially support the establishment of more tailored treatment approaches for patients with mCRC."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • KRAS

Leveraging tumor size and time to death from bevacizumab (BEV) historical data to predict overall survival in ovarian cancer patients treated with vanucizumab (VAN) (AACR 2018) - P1; "This approach shows the benefit of using TK modeling, when drugs show similar mechanism of action, in early phase to predict potential outcome of drug combination, not yet tested in patients. Leveraging historical data for the development of survival model integrating TK metrics can be used to inform the expected OS outcome in phase 3 and can provide a quantitative tool to evaluate the chance of drug success."

Clinical • Ovarian Cancer

Final results of the McCAVE trial: A double-blind, randomized phase 2 study of vanucizumab (VAN) plus FOLFOX vs. bevacizumab (BEV) plus FOLFOX in patients (pts) with previously untreated metastatic colorectal carcinoma (mCRC). (ASCO 2017) - P2; "The combination of VAN and FOLFOX did not improve PFS and was associated with a marked increase in hypertension compared with BEV plus FOLFOX. Our results strongly suggest that ANG-2 is not a relevant therapeutic target in the setting of first line mCRC."

Biomarker • Clinical • P2 data • Biosimilar • Cardiovascular • Colorectal Cancer • Hematological Malignancies • Venous Thromboembolism

Vanucizumab (VAN) in combination with atezolizumab (ATEZO) for platinum-resistant recurrent ovarian cancer (PROC): Results from a single arm extension phase of the phase I study BP28179 (ESMO 2017) - P1; "...VAN as a single agent showed an objective response rate (ORR) of 29% in bevacizumab- naïve PROC...Our data suggest that VAN plus ATEZO does not improve upon monotherapy with VAN or ATEZO in PROC. The safety profile of this combination is consistent with reports for the single agents in this setting."

Combination therapy • P1 data • Ovarian Cancer

Combination of subcutaneous selicrelumab (CD40 agonist) and vanucizumab (anti-Ang2/VEGF) in patients with solid tumors demonstrates early clinical activity and a favorable safety profile (SITC 2018) - P1; "Trial Registrationl This study is registered on Clinicaltrials.gov: NCT02665416 ; Background Selicrelumab is a fully human agonistic IgG2 monoclonal antibody to CD40, a member of the TNFreceptor superfamily expressed on antigenpresenting cells (APC), endothelial cells and some tumors. The combination demonstrated a favorable safety profile with no evidence for systemic autoimmune toxicity. The results triggered an expansion of the study in selected tumor indications with 16mg SC selicrelumab in combination with bevacizumab (anti- VEGF)."

Clinical • IO biomarker • Bladder Cancer • Genito-urinary Cancer • Gynecologic Cancers • Ovarian Cancer • Solid Tumor • Urothelial Cancer

Angiopoietin inhibitors: A review on targeting tumor angiogenesis. (PubMed, Eur J Pharmacol) - "Drugs studied in the article are selective as well as non-selective inhibitors of angiopoietin 2 like Trebananib (AMG 386), AMG 780, REGN 910, CVX 060, MEDI 3617 and dual inhibitors of angiopoietin 2 and VEGF like Vanucizumab and RG7716. The angiopoietin inhibitors show promising results alone and in combination with VEGF inhibitors in various malignancies."

Journal • Review • Immunology • Inflammation • Oncology

Vanucizumab mode of action: Serial biomarkers in plasma, tumor, and skin-wound-healing biopsies. (PubMed, Transl Oncol) - "Vanucizumab demonstrated a consistent biological effect on vascular-related biomarkers, confirming proof of concept. Skin-wound-healing biopsies were a valuable surrogate for studying angiogenesis-related mechanisms."

Biomarker • Journal • Oncology • Solid Tumor

A Study of the Safety and Efficacy of Atezolizumab Administered in Combination With Bevacizumab and/or Other Treatments in Participants With Solid Tumors (clinicaltrials.gov) - P1; N=430; Recruiting; Sponsor: Hoffmann-La Roche; Trial completion date: May 2019 ➔ Jan 2021

Trial completion date • Biosimilar • Gastric Cancer • Hepatocellular Cancer • Pancreatic Cancer

Longitudinal analysis of organ-specific tumor lesion sizes in metastatic colorectal cancer patients receiving first line standard chemotherapy in combination with anti-angiogenic treatment. (PubMed, J Pharmacokinet Pharmacodyn) - "Data were from the McCAVE trial, in which 189 previously untreated patients with metastatic colorectal carcinoma (mCRC) received either bevacizumab (control, C) or vanucizumab (experimental, E), on top of standard chemotherapy. This long period of tumor shrinkage associated with a slightly larger change from baseline at nadir (- 51.4% in lymph nodes and - 62.6% in 'other organs' in the group E, compared to - 46.2% and - 46.9% in group C) resulted in a clinically meaningful difference in the tumor dynamics of patients in group E compared to the group C. The proportion of variance explained by the inter-lesion variability for each model parameter was large (ranging between 10 and 56%), reflecting the heterogeneity in tumor dynamics across organs. These findings suggest that there is value in understanding both within- and between-patient variability in tumor size's time dynamics using an appropriate modeling framework, as this information..."

Clinical • Combination therapy • Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Roche: HY 2016 Results (Roche) - Anticipated initiation of P3 IMvigor 130 trial (NCT02807636) of Tecentriq + gemcitabine and carboplatin for 1L cisplatin-ineligible metastatic urothelial cancer in Q3 2016; Anticipated initiation of arm D in P1 trial (NCT02715531) of Tecentriq + vanucizumab/Avastin in HCC in Q3 2016; Anticipated data presentation from P1 trial (NCT01633970) in ovarian cancer at ESMO (October 7-11, 2016); Anticipated data presentation from P1 trial (NCT01988896) of Tecentriq + Cotellic in CRC at ESMO (October 7-11, 2016); Anticipated data presentation from P2 BIRCH trial (NCT02031458) in PDL1+ NSCLC at IASLC (December 4-7, 2016)

Anticipated P1 data • Anticipated P2 data • Anticipated trial initiation date • Trial status • Biosimilar • Colorectal Cancer • Hepatocellular Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer

Roche: J.P. Morgan Healthcare Conference (Roche, 35th Annual J.P. Morgan Healthcare Conference) - Anticipated data from P1 trial (NCT01688206) of Tecentriq in combination with vanucizumab for solid tumors in 2017; Anticipated data from P2 IMmotion 150 trial (NCT01984242) of Tecentriq in combination with Avastin for 1L RCC in 2017; Anticipated data from P3 IMpower 150 trial (NCT02366143) in 1L non-squamous NSCLC in Q3 2017

Anticipated P1 data • Anticipated P2 data • Anticipated P3 data • Biosimilar • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma

Roche: J.P. Morgan Healthcare Conference (Roche, 35th Annual J.P. Morgan Healthcare Conference) - Anticipated data from P1 trial (NCT01688206) of Tecentriq in combination with vanucizumab for solid tumors in 2017; Anticipated data from P2 IMmotion 150 trial (NCT01984242) of Tecentriq in combination with Avastin for 1L RCC in 2017; Anticipated data from P3 IMpower 150 trial (NCT02366143) in 1L non-squamous NSCLC in Q3 2017

Anticipated P1 data • Anticipated P2 data • Anticipated P3 data • Biosimilar • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma

Roche: Nine-month Sales 2016 Presentation (Roche) - Anticipated first patient for all-comer population in P3 IMpower 110 trial (NCT02409342) of Tecentriq monotherapy for adjuvant NSCLC in Q4 2016; Anticipated first patient in arm D of P1 trial (NCT02715531) of Tecentriq + Avastin/vanucizumab in HCC in Q4 2016; Anticipated first patient in P1/2 trial (NCT02729896) of Tecentriq + Rituxan + polatuzumab for DLBCL in Q1 2017

Trial status • Biosimilar • Diffuse Large B Cell Lymphoma • Gastrointestinal Cancer • Hematological Malignancies • Hepatocellular Cancer • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology

McCAVE: A Study Comparing the Efficacy and Safety of Vanucizumab and FOLFOX With Bevacizumab and FOLFOX in Participants With Untreated Metastatic Colorectal Cancer (clinicaltrials.gov) - P2; N=200; Active, not recruiting; Sponsor: Hoffmann-La Roche; Recruiting ➔ Active, not recruiting; Trial primary completion date: Dec 2017 ➔ Jul 2016

Enrollment closed • Trial primary completion date • Biosimilar • Colorectal Cancer • Gastrointestinal Cancer • Oncology

A Study of Vanucizumab (RO5520985) Alone or in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=132; Completed; Sponsor: Hoffmann-La Roche; Active, not recruiting ➔ Completed

Trial completion • Biosimilar • Ovarian Cancer

Roche: Q1 FY 2016 Results (Roche) - Anticipated NME submission in US for CRC in 2019 or later; Anticipated submission in EU for CRC in 2019 or later

Anticipated BLA • Anticipated EU regulatory • Colorectal Cancer • Oncology

Roche: Analyst Event at ASCO 2016 (Roche) - Anticipated data from P2 McCAVE trial (NCT02141295) of vanucizumab in combination with FOLFOX in 1L mCRC in late 2016

Anticipated P2 data • Colorectal Cancer • Oncology

Roche: J.P. Morgan Healthcare Conference (35th Annual J.P. Morgan Healthcare Conference, Roche) - Anticipated data from P1 trial (NCT02760797) of emactuzumab in combination with RO7009789 (aCD40) in advanced solid tumors in 2017; Anticipated data from P1 trial (NCT02665416) of vanucizumab in combination with RO7009789 in metastatic solid tumors in 2017

Anticipated P1 data • Oncology

Roche: J.P. Morgan Healthcare Conference (35th Annual J.P. Morgan Healthcare Conference, Roche) - Anticipated data from P1 trial (NCT02760797) of emactuzumab in combination with RO7009789 (aCD40) in advanced solid tumors in 2017; Anticipated data from P1 trial (NCT02665416) of vanucizumab in combination with RO7009789 in metastatic solid tumors in 2017

Anticipated P1 data • Oncology

Results from the first-in-human (FIH) phase I study of RO5520985 (RG7221), a novel bispecific human anti-ANG-2/anti-VEGF-A antibody, administered as an intravenous infusion to patients with advanced solid tumors (ASCO 2014) - Presentation time: Friday, May 30; 1:00 PM - 4:00 PM; Abstract #2525; P1, N=42; NCT01688206; Sponsor: Hoffmann-La Roche; "The most frequent AE of any grade (G) were hypertension (50%), asthenia (36%), headache (29%) and fatigue (19%). Most common AE ≥ G3 was hypertension (19%), predominantly associated with the weekly regimen (QW 30% vs. 9% Q2W)...The progression-free rate at 8 weeks was 67% (Q2W) and 53% (QW)."

P1 data • Oncology

A Study Comparing the Efficacy and Safety of Vanucizumab and FOLFOX With Bevacizumab and FOLFOX in Participants With Untreated Metastatic Colorectal Cancer (clinicaltrials.gov) - P2; N=197; Terminated; Sponsor: Hoffmann-La Roche; Completed ➔ Terminated

Clinical • Trial termination

The McCAVE Trial: Vanucizumab plus mFOLFOX-6 Versus Bevacizumab plus mFOLFOX-6 in Patients with Previously Untreated Metastatic Colorectal Carcinoma (mCRC). (PubMed, Oncologist) - "This randomized phase II study demonstrates that additional angiopoietin-2 (Ang-2) inhibition does not result in superior benefit over anti-VEGF-A blockade alone when each added to standard chemotherapy. Moreover, the performed pharmacokinetic and pharmacodynamic analysis revealed that vanucizumab was bioavailable and affected its intended target, thereby strongly suggesting that Ang-2 is not a relevant therapeutic target in the clinical setting of treatment-naïve metastatic colorectal cancer. As a result, the further clinical development of the dual VEGF-A and Ang-2 inhibitor vanucizumab was discontinued."

Clinical • Journal

Efficacy of a Bispecific Antibody Co-Targeting VEGFA and Ang-2 in Combination with Chemotherapy in a Chemoresistant Colorectal Carcinoma Xenograft Model. (PubMed, Molecules) - "Vascular endothelial growth factor (VEGF) inhibition by the addition of bevacizumab to the chemotherapy regimen of metastatic colorectal cancer leads to an improved outcome...Chemotherapy consisted of 5-FU and irinotecan...In conclusion, the data from this model clearly support the strategy of co-targeting VEGF and Ang-2 and further demonstrate the beneficial impact of co-treatment with chemotherapy. The clear superiority of the CrossMab-containing regimen compared to clinical standard anti-VEGF/chemotherapy warrants further analyses in other models."

Combination therapy • Journal • Preclinical

Study Evaluating the Safety, Pharmacokinetics (PK), Pharmacodynamics (PD), and Therapeutic Activity of Selicrelumab (RO7009789) With Vanucizumab or Bevacizumab in Participants With Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=94; Completed; Sponsor: Hoffmann-La Roche; Active, not recruiting ➔ Completed

Clinical • Combination therapy • Trial completion